Cocrystals, pharmaceutical compositions thereof, and methods of treatment involving same
Inventors
Lane, Benjamin S. • Gu, Chong-Hui
Assignees
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Publication Number
US-11851417-B2
Publication Date
2023-12-26
Expiration Date
Abstract
Provided are solid forms of a compound useful for treating cancer, pharmaceutical compositions thereof, and methods of treating cancer comprising administering the solid forms described herein to a patient in need thereof.
Core Innovation
The invention relates to a cocrystal comprising a compound of formula (I) and maleic acid. The cocrystal is characterized using XRPD and DSC thermograms, with specified diffraction peak positions and endothermic onset temperatures, and embodiments specify a 1:1 stoichiometric molar ratio of the compound of formula (I) and maleic acid.
The disclosure addresses solid forms of an IDH1/IDH2-mutant cancer therapeutic and identifies isocitrate dehydrogenase 1 (IDH1) and isocitrate dehydrogenase 2 (IDH2) enzymes as producing 2-hydroxyglutarate (2HG). The document further describes that mutant IDH1/IDH2 enzymes accumulate 2-hydroxyglutarate (2HG), and that the active compound is a compound of formula (I).
The solid-form embodiments include cocrystals, free crystalline forms, solvent-bound forms, and amorphous solid dispersions, including polymer-based solid dispersions and HPMCAS. Specific embodiments include a citric acid cocrystal type A and a maleic acid cocrystal type A, each described with defined XRPD/DSC features, together with pharmaceutical compositions and treatment methods tied to the 2HG-related rationale.
Claims Coverage
The claim coverage centers on a maleic acid cocrystal comprising a compound of formula (I), with additional inventive features for analytical characterization, stoichiometric definition, and treatment of cancers associated with IDH1 or IDH2 mutations. In total, six inventive features are represented across the merged materials.
Maleic acid cocrystal of compound of formula (I)
A cocrystal comprising a compound of formula (I) and maleic acid.
X-ray powder diffraction pattern characterization
The cocrystal is characterized by an X-ray powder diffraction pattern collected in reflection mode with at least one diffraction peak at a specified 2-theta position within ±0.2 degrees 2-theta.
Differential scanning calorimetry onset temperatures
The cocrystal is characterized by a differential scanning calorimetry thermogram with endothermic peaks at onset temperatures of 91.2°C and 128.4°C (±2.0°C).
Stoichiometric 1:1 molar ratio
The compound of formula (I) and maleic acid are present in a 1:1 molar ratio.
Treatment of cancer with IDH1/IDH2 mutations
A method for treating cancer in a patient having an IDH1 or IDH2 mutation by administering a therapeutically effective amount of the cocrystal.
Defined daily dosage options based on compound of formula (I)
Administering the cocrystal, drug substance, or pharmaceutical composition in an amount of about 10 mg, about 25 mg, about 50 mg, about 100 mg, about 200 mg, or about 300 mg per day, based on the amount of the compound of formula (I).
The inventive coverage centers on a maleic acid cocrystal of a compound of formula (I), defined by XRPD and DSC characterization and a specified 1:1 molar ratio. The coverage further includes treatment of cancers associated with IDH1 or IDH2 mutations by administering therapeutically effective amounts, with example daily dose options tied to the amount of the compound of formula (I).
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer in a patient having an IDH1 mutation or an IDH2 mutation by administering a therapeutically effective amount of the cocrystal.
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